000117263 001__ 117263
000117263 005__ 20240319081016.0
000117263 0247_ $$2doi$$a10.3390/antiox11061110
000117263 0248_ $$2sideral$$a128988
000117263 037__ $$aART-2022-128988
000117263 041__ $$aeng
000117263 100__ $$aPacheco-Garcia, Juan Luis
000117263 245__ $$aAllosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations
000117263 260__ $$c2022
000117263 5060_ $$aAccess copy available to the general public$$fUnrestricted
000117263 5203_ $$aAllosterism is a common phenomenon in protein biochemistry that allows rapid regulation of protein stability; dynamics and function. However, the mechanisms by which allosterism occurs (by mutations or post-translational modifications (PTMs)) may be complex, particularly due to long-range propagation of the perturbation across protein structures. In this work, we have investigated allosteric communication in the multifunctional, cancer-related and antioxidant protein NQO1 by mutating several fully buried leucine residues (L7, L10 and L30) to smaller residues (V, A and G) at sites in the N-terminal domain. In almost all cases, mutated residues were not close to the FAD or the active site. Mutations L\u2192G strongly compromised conformational stability and solubility, and L30A and L30V also notably decreased solubility. The mutation L10A, closer to the FAD binding site, severely decreased FAD binding affinity (\u224820 fold vs. WT) through long-range and context-dependent effects. Using a combination of experimental and computational analyses, we show that most of the effects are found in the apo state of the protein, in contrast to other common polymorphisms and PTMs previously characterized in NQO1. The integrated study presented here is a first step towards a detailed structural-functional mapping of the mutational landscape of NQO1, a multifunctional and redox signaling protein of high biomedical relevance.
000117263 536__ $$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E35-20R$$9info:eu-repo/grantAgreement/ES/ERDF-B-BIO-84-UGR20$$9info:eu-repo/grantAgreement/EC/H2020/82383/EPIC-XS/EU$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 82383 EPIC-XS$$9info:eu-repo/grantAgreement/ES/JA-P18-RT-2413$$9info:eu-repo/grantAgreement/ES/MCIU-ERDF/RTI2018-096246-B-I00$$9info:eu-repo/grantAgreement/ES/MICINN-AEI/PID2019-103901GB-I00
000117263 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000117263 590__ $$a7.0$$b2022
000117263 592__ $$a1.084$$b2022
000117263 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b46 / 285 = 0.161$$c2022$$dQ1$$eT1
000117263 593__ $$aBiochemistry$$c2022$$dQ1
000117263 591__ $$aFOOD SCIENCE & TECHNOLOGY$$b13 / 142 = 0.092$$c2022$$dQ1$$eT1
000117263 593__ $$aClinical Biochemistry$$c2022$$dQ1
000117263 591__ $$aCHEMISTRY, MEDICINAL$$b6 / 60 = 0.1$$c2022$$dQ1$$eT1
000117263 593__ $$aFood Science$$c2022$$dQ1
000117263 593__ $$aPhysiology$$c2022$$dQ1
000117263 593__ $$aMolecular Biology$$c2022$$dQ2
000117263 593__ $$aCell Biology$$c2022$$dQ2
000117263 594__ $$a8.8$$b2022
000117263 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000117263 700__ $$aLoginov, Dmitry S.
000117263 700__ $$0(orcid)0000-0002-6649-9153$$aAnoz-Carbonell, Ernesto
000117263 700__ $$aVankova, Pavla
000117263 700__ $$aPalomino-Morales, Rogelio
000117263 700__ $$aSalido, Eduardo
000117263 700__ $$aMan, Petr
000117263 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, Milagros$$uUniversidad de Zaragoza
000117263 700__ $$aNaganathan, Athi N.
000117263 700__ $$aPey, Angel L.
000117263 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000117263 773__ $$g11, 6 (2022), 1110$$pAntioxidants$$tAntioxidants$$x2076-3921
000117263 8564_ $$s4370878$$uhttps://zaguan.unizar.es/record/117263/files/texto_completo.pdf$$yVersión publicada
000117263 8564_ $$s2740188$$uhttps://zaguan.unizar.es/record/117263/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000117263 909CO $$ooai:zaguan.unizar.es:117263$$particulos$$pdriver
000117263 951__ $$a2024-03-18-15:40:05
000117263 980__ $$aARTICLE